Potentiation of RSV disease was observed in cotton rats (Sigmodon hispidus) previously immunized with formalin- inactivated RSV. This potentiation of disease resembled that observed 20 years ago during a clinical trial of formalin- inactivated RSV vaccine in young infants. Animals immunized with the Lot 100 RSV vaccine used in the clinical trials of 20 year ago, or with freshly-prepared, formalin-killed RSV, were challenged intranasally with RSV. Accentuated pulmonary pathology developed when these animals were infected with RSV. This potentiated response was characterized by polymorphonuclear and lymphocytic infiltration of the lungs, which began one day after viral challenge. Analysis of this phenomenon indicated that IgG and C3 were deposited in both the lungs and kidneys. Also pulmonary pathology was less severe in complement-depleted animals. Significantly, a dose-response effect was observed which was similar to that described for experimental immune complex disease. These observations suggested that the potentiated disease caused by formalin- inactivated RSV vaccine was in part the result of a pulmonary Arthus reaction. Efforts begun 8 years ago in our laboratory have recently yielded an inbred strain of cotton rat, which can now be used for studies of the cellular basis of vaccine-induced disease potentiation.